Artículo

Inchauspe, C.G.; Urbano, F.J.; Di Guilmi, M.N.; Ferrari, M.D.; van den Maagdenberg, A.M.J.M.; Forsythe, I.D.; Uchitel, O.D. "Presynaptic Cav2.1 calcium channels carrying familial hemiplegic migraine mutation R192Q allow faster recovery from synaptic depression in mouse calyx of Held" (2012) Journal of Neurophysiology. 108(11):2967-2976
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Abstract:

CaV2.1 Ca2+ channels have a dominant and specific role in initiating fast synaptic transmission at central excitatory synapses, through a close association between release sites and calcium sensors. Familial hemiplegic migraine type 1 (FHM-1) is an autosomal-dominant subtype of migraine with aura, caused by missense mutations in the CACNA1A gene that encodes the α1A pore-forming subunit of CaV2.1 channel. We used knock-in (KI) transgenic mice harboring the FHM-1 mutation R192Q to study the consequences of this mutation in neurotransmission at the giant synapse of the auditory system formed by the presynaptic calyx of Held terminal and the postsynaptic neurons of the medial nucleus of the trapezoid body (MNTB). Although synaptic transmission seems unaffected by low-frequency stimulation in physiological Ca2+ concentration, we observed that with low Ca2+ concentrations (<1 mM) excitatory postsynaptic currents (EPSCs) showed increased amplitudes in R192Q KI mice compared with wild type (WT), meaning significant differences in the nonlinear calcium dependence of nerve-evoked transmitter release. In addition, when EPSCs were evoked by broadened presynaptic action potentials (achieved by inhibition of K+ channels) via Cav2.1-triggered exocytosis, R192Q KI mice exhibited further enhancement of EPSC amplitude and charge compared with WT mice. Repetitive stimulation of afferent axons to the MNTB at different frequencies caused short-term depression of EPSCs that recovered significantly faster in R192Q KI mice than in WT mice. Faster recovery in R192Q KI mice was prevented by the calcium chelator EGTA-AM, pointing to enlarged residual calcium as a key factor in accelerating the replenishment of synaptic vesicles. © 2012 the American Physiological Society.

Registro:

Documento: Artículo
Título:Presynaptic Cav2.1 calcium channels carrying familial hemiplegic migraine mutation R192Q allow faster recovery from synaptic depression in mouse calyx of Held
Autor:Inchauspe, C.G.; Urbano, F.J.; Di Guilmi, M.N.; Ferrari, M.D.; van den Maagdenberg, A.M.J.M.; Forsythe, I.D.; Uchitel, O.D.
Filiación:Instituto de Fisiología, Biología molecular y Neurociencias, CONICET, Departamento de Fisiología, Biología Molecular y Celular, Facultad de Ciencias Exactas y Naturales Universidad de Buenos Aires, Buenos Aires, Argentina
Department of Neurology, Leiden University Medical Centre, Leiden, Netherlands
Department of Human Genetics, Leiden University Medical Centre, Leiden, Netherlands
Department of Cell Physiology and Pharmacology, University of Leicester, Leicester, United Kingdom
Palabras clave:Cav2.1 channels; Excitatory postsynaptic currents; Familial hemiplegic migraine; R192Q knock-in mice; Short-term synaptic plasticity; arginine; calcium; egtazic acid; glutamine; potassium channel; unclassified drug; voltage gated calcium channel; voltage gated calcium channel 2.1; Cacna1a protein, mouse; calcium channel P type; calcium channel Q type; chelating agent; glutamic acid; potassium channel blocking agent; action potential; animal cell; animal tissue; article; calyx of Held; excitatory postsynaptic potential; exocytosis; familial hemiplegic migraine; gene mutation; long term depression; medial nucleus of the trapezoid body; mouse; nerve cell; nerve fiber; nerve stimulation; neurotransmitter release; nonhuman; presynaptic nerve; priority journal; synapse vesicle; synaptic transmission; transgenic mouse; wild type; animal; auditory nervous system; cerebellar ataxia; cytology; excitatory postsynaptic potential; genetics; metabolism; migraine; missense mutation; nerve cell plasticity; physiology; pons; sensory nerve cell; synaptosome; Action Potentials; Animals; Auditory Pathways; Calcium; Calcium Channels, P-Type; Calcium Channels, Q-Type; Cerebellar Ataxia; Chelating Agents; Excitatory Postsynaptic Potentials; Exocytosis; Glutamic Acid; Mice; Mice, Transgenic; Migraine Disorders; Mutation, Missense; Neuronal Plasticity; Neurons, Afferent; Pons; Potassium Channel Blockers; Presynaptic Terminals
Año:2012
Volumen:108
Número:11
Página de inicio:2967
Página de fin:2976
DOI: http://dx.doi.org/10.1152/jn.01183.2011
Título revista:Journal of Neurophysiology
Título revista abreviado:J. Neurophysiol.
ISSN:00223077
CODEN:JONEA
CAS:arginine, 1119-34-2, 15595-35-4, 7004-12-8, 74-79-3; calcium, 14092-94-5, 7440-70-2; egtazic acid, 67-42-5; glutamine, 56-85-9, 6899-04-3; glutamic acid, 11070-68-1, 138-15-8, 56-86-0, 6899-05-4; Cacna1a protein, mouse; Calcium, 7440-70-2; Calcium Channels, P-Type; Calcium Channels, Q-Type; Chelating Agents; Glutamic Acid, 56-86-0; Potassium Channel Blockers
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00223077_v108_n11_p2967_Inchauspe

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Citas:

---------- APA ----------
Inchauspe, C.G., Urbano, F.J., Di Guilmi, M.N., Ferrari, M.D., van den Maagdenberg, A.M.J.M., Forsythe, I.D. & Uchitel, O.D. (2012) . Presynaptic Cav2.1 calcium channels carrying familial hemiplegic migraine mutation R192Q allow faster recovery from synaptic depression in mouse calyx of Held. Journal of Neurophysiology, 108(11), 2967-2976.
http://dx.doi.org/10.1152/jn.01183.2011
---------- CHICAGO ----------
Inchauspe, C.G., Urbano, F.J., Di Guilmi, M.N., Ferrari, M.D., van den Maagdenberg, A.M.J.M., Forsythe, I.D., et al. "Presynaptic Cav2.1 calcium channels carrying familial hemiplegic migraine mutation R192Q allow faster recovery from synaptic depression in mouse calyx of Held" . Journal of Neurophysiology 108, no. 11 (2012) : 2967-2976.
http://dx.doi.org/10.1152/jn.01183.2011
---------- MLA ----------
Inchauspe, C.G., Urbano, F.J., Di Guilmi, M.N., Ferrari, M.D., van den Maagdenberg, A.M.J.M., Forsythe, I.D., et al. "Presynaptic Cav2.1 calcium channels carrying familial hemiplegic migraine mutation R192Q allow faster recovery from synaptic depression in mouse calyx of Held" . Journal of Neurophysiology, vol. 108, no. 11, 2012, pp. 2967-2976.
http://dx.doi.org/10.1152/jn.01183.2011
---------- VANCOUVER ----------
Inchauspe, C.G., Urbano, F.J., Di Guilmi, M.N., Ferrari, M.D., van den Maagdenberg, A.M.J.M., Forsythe, I.D., et al. Presynaptic Cav2.1 calcium channels carrying familial hemiplegic migraine mutation R192Q allow faster recovery from synaptic depression in mouse calyx of Held. J. Neurophysiol. 2012;108(11):2967-2976.
http://dx.doi.org/10.1152/jn.01183.2011